Network controllability solutions for computational drug repurposing using genetic algorithms

Sci Rep. 2022 Jan 26;12(1):1437. doi: 10.1038/s41598-022-05335-3.

Abstract

Control theory has seen recently impactful applications in network science, especially in connections with applications in network medicine. A key topic of research is that of finding minimal external interventions that offer control over the dynamics of a given network, a problem known as network controllability. We propose in this article a new solution for this problem based on genetic algorithms. We tailor our solution for applications in computational drug repurposing, seeking to maximize its use of FDA-approved drug targets in a given disease-specific protein-protein interaction network. We demonstrate our algorithm on several cancer networks and on several random networks with their edges distributed according to the Erdős-Rényi, the Scale-Free, and the Small World properties. Overall, we show that our new algorithm is more efficient in identifying relevant drug targets in a disease network, advancing the computational solutions needed for new therapeutic and drug repurposing approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Computational Biology / methods
  • Drug Repositioning / methods*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Prescription Drugs / therapeutic use
  • Protein Interaction Maps / drug effects

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Prescription Drugs